| Structural highlights
2w6v is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , , ,
| | Related: | 1xzv, 1fn3, 1y4p, 1hba, 1lfl, 1lfz, 1y4f, 1o1l, 1o1n, 2hbf, 1cbm, 1bab, 1a3o, 1dke, 1dxt, 1a9w, 2hhd, 1j7y, 1j3y, 1bij, 2dn2, 1hgb, 2hbd, 1aj9, 1xxt, 1hbs, 1aby, 1abw, 1lft, 1yev, 1jy7, 1r1y, 1yhr, 1yeq, 1rvw, 1hab, 1gbv, 1yen, 1j40, 1hco, 1y45, 1nej, 1gli, 1cls, 1y0d, 1yg5, 2dn3, 1ye1, 2hbc, 1bz0, 1sdl, 1y85, 1a01, 1gzx, 1c7c, 1qi8, 1rps, 1yie, 1o1i, 1lfv, 1xy0, 1a0z, 1ird, 2d60, 1y46, 1xz4, 1hac, 1xz7, 1j7s, 1dxu, 1o1k, 1y2z, 1kd2, 1xz2, 2hbs, 1hgc, 1mko, 1rq4, 1a3n, 1hbb, 1y01, 2hco, 1buw, 1cbl, 1yff, 1hho, 1xz5, 1y7g, 1yh9, 1ye2, 1yzi, 1b86, 1y7c, 1yhe, 1qsh, 1y4q, 1ch4, 1ygf, 1y09, 1c7b, 1y5j, 2d5z, 2hhe, 1vwt, 1qxe, 1coh, 1j41, 1y4g, 1y35, 1o1o, 1y0t, 1shr, 1m9p, 1o1p, 1rqa, 1xzu, 1uiw, 1yvq, 1ygd, 1lfy, 1hga, 1lfq, 1y83, 1y22, 1bbb, 1y4b, 1gbu, 1k0y, 1y7z, 1ljw, 1yeo, 1qxd, 1y31, 1y0a, 1bz1, 1y0c, 1z8u, 1yih, 1sdk, 1a00, 1y7d, 1nqp, 2dn1, 1xye, 1k1k, 6hbw, 1ye0, 1nih, 4hhb, 1y4v, 1c7d, 1y8w, 1y0w, 1a0u, 1g9v, 1bzz, 1hdb, 1fdh, 1ydz, 1thb, 1cmy, 1yeu, 1y5f, 1r1x, 1qsi, 1si4, 1y4r, 1j7w, 2hbe, 1o1m, 1yvt, 1j3z, 1y5k, 1dxv, 1rq3, 1o1j, 2w6w, 2w6y, 2w6x, 2w72 |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
Disease
[HBA_HUMAN] Defects in HBA1 may be a cause of Heinz body anemias (HEIBAN) [MIM:140700]. This is a form of non-spherocytic hemolytic anemia of Dacie type 1. After splenectomy, which has little benefit, basophilic inclusions called Heinz bodies are demonstrable in the erythrocytes. Before splenectomy, diffuse or punctate basophilia may be evident. Most of these cases are probably instances of hemoglobinopathy. The hemoglobin demonstrates heat lability. Heinz bodies are observed also with the Ivemark syndrome (asplenia with cardiovascular anomalies) and with glutathione peroxidase deficiency.[1] Defects in HBA1 are the cause of alpha-thalassemia (A-THAL) [MIM:604131]. The thalassemias are the most common monogenic diseases and occur mostly in Mediterranean and Southeast Asian populations. The hallmark of alpha-thalassemia is an imbalance in globin-chain production in the adult HbA molecule. The level of alpha chain production can range from none to very nearly normal levels. Deletion of both copies of each of the two alpha-globin genes causes alpha(0)-thalassemia, also known as homozygous alpha thalassemia. Due to the complete absence of alpha chains, the predominant fetal hemoglobin is a tetramer of gamma-chains (Bart hemoglobin) that has essentially no oxygen carrying capacity. This causes oxygen starvation in the fetal tissues leading to prenatal lethality or early neonatal death. The loss of three alpha genes results in high levels of a tetramer of four beta chains (hemoglobin H), causing a severe and life-threatening anemia known as hemoglobin H disease. Untreated, most patients die in childhood or early adolescence. The loss of two alpha genes results in mild alpha-thalassemia, also known as heterozygous alpha-thalassemia. Affected individuals have small red cells and a mild anemia (microcytosis). If three of the four alpha-globin genes are functional, individuals are completely asymptomatic. Some rare forms of alpha-thalassemia are due to point mutations (non-deletional alpha-thalassemia). The thalassemic phenotype is due to unstable globin alpha chains that are rapidly catabolized prior to formation of the alpha-beta heterotetramers. Note=Alpha(0)-thalassemia is associated with non-immune hydrops fetalis, a generalized edema of the fetus with fluid accumulation in the body cavities due to non-immune causes. Non-immune hydrops fetalis is not a diagnosis in itself but a symptom, a feature of many genetic disorders, and the end-stage of a wide variety of disorders. Defects in HBA1 are the cause of hemoglobin H disease (HBH) [MIM:613978]. HBH is a form of alpha-thalassemia due to the loss of three alpha genes. This results in high levels of a tetramer of four beta chains (hemoglobin H), causing a severe and life-threatening anemia. Untreated, most patients die in childhood or early adolescence.[2] [HBB_HUMAN] Defects in HBB may be a cause of Heinz body anemias (HEIBAN) [MIM:140700]. This is a form of non-spherocytic hemolytic anemia of Dacie type 1. After splenectomy, which has little benefit, basophilic inclusions called Heinz bodies are demonstrable in the erythrocytes. Before splenectomy, diffuse or punctate basophilia may be evident. Most of these cases are probably instances of hemoglobinopathy. The hemoglobin demonstrates heat lability. Heinz bodies are observed also with the Ivemark syndrome (asplenia with cardiovascular anomalies) and with glutathione peroxidase deficiency.[3] [4] [5] [6] Defects in HBB are the cause of beta-thalassemia (B-THAL) [MIM:613985]. A form of thalassemia. Thalassemias are common monogenic diseases occurring mostly in Mediterranean and Southeast Asian populations. The hallmark of beta-thalassemia is an imbalance in globin-chain production in the adult HbA molecule. Absence of beta chain causes beta(0)-thalassemia, while reduced amounts of detectable beta globin causes beta(+)-thalassemia. In the severe forms of beta-thalassemia, the excess alpha globin chains accumulate in the developing erythroid precursors in the marrow. Their deposition leads to a vast increase in erythroid apoptosis that in turn causes ineffective erythropoiesis and severe microcytic hypochromic anemia. Clinically, beta-thalassemia is divided into thalassemia major which is transfusion dependent, thalassemia intermedia (of intermediate severity), and thalassemia minor that is asymptomatic.[7] Defects in HBB are the cause of sickle cell anemia (SKCA) [MIM:603903]; also known as sickle cell disease. Sickle cell anemia is characterized by abnormally shaped red cells resulting in chronic anemia and periodic episodes of pain, serious infections and damage to vital organs. Normal red blood cells are round and flexible and flow easily through blood vessels, but in sickle cell anemia, the abnormal hemoglobin (called Hb S) causes red blood cells to become stiff. They are C-shaped and resembles a sickle. These stiffer red blood cells can led to microvascular occlusion thus cutting off the blood supply to nearby tissues. Defects in HBB are the cause of beta-thalassemia dominant inclusion body type (B-THALIB) [MIM:603902]. An autosomal dominant form of beta thalassemia characterized by moderate anemia, lifelong jaundice, cholelithiasis and splenomegaly, marked morphologic changes in the red cells, erythroid hyperplasia of the bone marrow with increased numbers of multinucleate red cell precursors, and the presence of large inclusion bodies in the normoblasts, both in the marrow and in the peripheral blood after splenectomy.[8]
Function
[HBA_HUMAN] Involved in oxygen transport from the lung to the various peripheral tissues. [HBB_HUMAN] Involved in oxygen transport from the lung to the various peripheral tissues.[9] LVV-hemorphin-7 potentiates the activity of bradykinin, causing a decrease in blood pressure.[10]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Our aim is to shed light on the conservation of potential ligand docking sites that play an important role in ligand dynamics of globins by using the technique of filling with xenon atoms internal cavities, naturally present in hemoglobin and myoglobin. In particular, we present the high resolution structures of the Xe-adduct of deoxygenated wild type human hemoglobin and a quadruple mutant (L(B10)Y and H(E7)Q in alpha and beta chains). For the sake of comparison we also determined under the same experimental conditions the xenon complex of wild type sperm whale myoglobin.The analysis revealed that the number and position of Xe binding cavities is different in the alpha and beta subunits, the latter being more similar to myoglobin. Notably no proximal Xe docking site was detected in hemoglobin, at variance with myoglobin. The pattern of internal cavities accessibility and affinity for xenon suggests a different role for the dynamics of ligand migration in the two types of hemoglobin chains as compared to myoglobin. The number and position of hydrophobic cavities in hemoglobin is briefly discussed also in comparison with the data available for other members of the globin superfamily. (c) 2009 Wiley Periodicals, Inc. Biopolymers, 2009.
Pattern of cavities in globins: The case of human hemoglobin.,Savino C, Miele AE, Draghi F, Johnson KA, Sciara G, Brunori M, Vallone B Biopolymers. 2009 Apr 13. PMID:19365817[11]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Ohba Y, Yamamoto K, Hattori Y, Kawata R, Miyaji T. Hyperunstable hemoglobin Toyama [alpha 2 136(H19)Leu----Arg beta 2]: detection and identification by in vitro biosynthesis with radioactive amino acids. Hemoglobin. 1987;11(6):539-56. PMID:2833478
- ↑ Traeger-Synodinos J, Harteveld CL, Kanavakis E, Giordano PC, Kattamis C, Bernini LF. Hb Aghia Sophia [alpha62(E11)Val-->0 (alpha1)], an "in-frame" deletion causing alpha-thalassemia. Hemoglobin. 1999 Nov;23(4):317-24. PMID:10569720
- ↑ Thillet J, Cohen-Solal M, Seligmann M, Rosa J. Functional and physicochemical studies of hemoglobin St. Louis beta 28 (B10) Leu replaced by Gln: a variant with ferric beta heme iron. J Clin Invest. 1976 Nov;58(5):1098-1106. PMID:186485 doi:http://dx.doi.org/10.1172/JCI108561
- ↑ Rahbar S, Feagler RJ, Beutler E. Hemoglobin Hammersmith (beta 42 (CD1) Phe replaced by Ser) associated with severe hemolytic anemia. Hemoglobin. 1981;5(1):97-105. PMID:6259091
- ↑ Blouquit Y, Bardakdjian J, Lena-Russo D, Arous N, Perrimond H, Orsini A, Rosa J, Galacteros F. Hb Bruxelles: alpha 2A beta (2)41 or 42(C7 or CD1)Phe deleted. Hemoglobin. 1989;13(5):465-74. PMID:2599881
- ↑ Rees DC, Rochette J, Schofield C, Green B, Morris M, Parker NE, Sasaki H, Tanaka A, Ohba Y, Clegg JB. A novel silent posttranslational mechanism converts methionine to aspartate in hemoglobin Bristol (beta 67[E11] Val-Met->Asp). Blood. 1996 Jul 1;88(1):341-8. PMID:8704193
- ↑ Thein SL, Hesketh C, Taylor P, Temperley IJ, Hutchinson RM, Old JM, Wood WG, Clegg JB, Weatherall DJ. Molecular basis for dominantly inherited inclusion body beta-thalassemia. Proc Natl Acad Sci U S A. 1990 May;87(10):3924-8. PMID:1971109
- ↑ Thein SL, Hesketh C, Taylor P, Temperley IJ, Hutchinson RM, Old JM, Wood WG, Clegg JB, Weatherall DJ. Molecular basis for dominantly inherited inclusion body beta-thalassemia. Proc Natl Acad Sci U S A. 1990 May;87(10):3924-8. PMID:1971109
- ↑ Ianzer D, Konno K, Xavier CH, Stocklin R, Santos RA, de Camargo AC, Pimenta DC. Hemorphin and hemorphin-like peptides isolated from dog pancreas and sheep brain are able to potentiate bradykinin activity in vivo. Peptides. 2006 Nov;27(11):2957-66. Epub 2006 Aug 9. PMID:16904236 doi:S0196-9781(06)00309-3
- ↑ Ianzer D, Konno K, Xavier CH, Stocklin R, Santos RA, de Camargo AC, Pimenta DC. Hemorphin and hemorphin-like peptides isolated from dog pancreas and sheep brain are able to potentiate bradykinin activity in vivo. Peptides. 2006 Nov;27(11):2957-66. Epub 2006 Aug 9. PMID:16904236 doi:S0196-9781(06)00309-3
- ↑ Savino C, Miele AE, Draghi F, Johnson KA, Sciara G, Brunori M, Vallone B. Pattern of cavities in globins: The case of human hemoglobin. Biopolymers. 2009 Apr 13. PMID:19365817 doi:10.1002/bip.21201
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